Sie befinden Sich nicht im Netzwerk der Universität Paderborn. Der Zugriff auf elektronische Ressourcen ist gegebenenfalls nur via VPN oder Shibboleth (DFN-AAI) möglich. mehr Informationen...
Combination of anti‐ CD 4 antibody treatment and donor lymphocyte infusion ameliorates graft‐ versus ‐host disease while preserving graft‐ versus ‐tumor effects in murine allogeneic hematopoietic stem cell transplantation
Ist Teil von
Cancer science, 2017-10, Vol.108 (10), p.1967-1973
Ort / Verlag
Tokyo: John Wiley & Sons, Inc
Erscheinungsjahr
2017
Quelle
Wiley Online Library
Beschreibungen/Notizen
Allogeneic hematopoietic stem cell transplantation (allo‐
HSCT
) is not only a well‐established immunotherapy for hematologic malignancies, but is potentially useful for treating solid tumors refractory to available therapies. However, application of allo‐
HSCT
to solid tumors is limited, despite the beneficial antitumor effects, by the risk of graft‐
versus
‐host disease (
GVHD
).
CD
4
+
T cells have been implicated in several aspects of
GVHD
, and suppress antitumor
CD
8
+
T‐cell responses. In the present study, we investigated clinically applicable allo‐
HSCT
protocols designed to maximize antitumor effects while reducing the risk of
GVHD
. We used a mouse model of allo‐
HSCT
with s.c. tumors. We found that myeloablative conditioning was associated with better inhibition of tumor growth but with severe acute
GVHD
. Early treatment with anti‐
CD
4
mA
b substantially ameliorated
GVHD
while preserving antitumor effects, leading to improved survival in myeloablative allo‐
HSCT
. Late treatment with anti‐
CD
4
mA
b also ameliorated
GVHD
to some extent. Donor lymphocyte infusion in
GVHD
mice treated with anti‐
CD
4
mA
b further suppressed tumor growth without exacerbating
GVHD
. Collectively, our results suggest that myeloablative allo‐
HSCT
followed by anti‐
CD
4
mA
b treatment and donor lymphocyte infusion could be a potent and safe immunotherapy for patients with cancers refractory to available therapies.